An Antarctic marine tunicate, Synoicum adareanum, is the source of a material, called “palmerolide A,” which was characterized as a differential cytotoxin, with an activity profile that correlated to V-ATPase inhibitors. J. Am. Chem. Soc. 2006, 128, 5630. Subsequent in vitro studies confirmed that palmerolide A indeed is a potent inhibitor of ATPases, in particular, bovine brain V-ATPase (IC50˜2 nM), and is a selective cytotoxin toward several cancer cell lines including melanoma, colon cancer, and renal cancer. Id.; U.S. Published Application No. 2005-0187286, the only portions of which are incorporated by reference, are those describing the inhibitory effects of Palmerolide A; and J. Biol. Chem. 2004, 279, 19755.
Palmerolide A was obtained from an organism found in one of the most remote areas of the world. Access from natural sources is severely limited by this fact and by the effective prohibition, via international treaty, of commercial exploitation in the Antarctic. A total synthesis is needed, therefore, to realize the promising antitumor properties of palmerolides.